The effect of PAP on UACR and metabolic indexes in patients with MS and OSAHS.

PURPOSE: To investigate the effects of positive airway pressure (PAP) device on urinary albumin to creatinine ratio (UACR) and metabolic indexes in patients with metabolic syndrome (MS) and obstructive sleep apnea-hypopnea syndrome (OSAHS). METHODS: This study is a retrospective cohort study. Grouped according to whether to use PAP treatment, there were 25 cases in the PAP group and 44 cases in the no OSAHS treatment group. The PAP group received positive airway pressure device and routine treatment of MS. The no OSAHS treatment group received routine treatment of OSAHS and MS. The treatment period is 3 months. RESULTS: 1. The PAP group demonstrated significant reductions in Body Mass Index (BMI), Waist circumference (WC), Neck circumference (NC), Visceral fat area (VFA), Fasting C peptide (FCP), high-sensitivity C-reactive protein (hs-CRP), and UACR compared to the no OSAHS treatment group, with significant differences (P all <0.05). Among them, the UACR in the PAP group decreased significantly (from 86.05(52.55,131.61)mg/g to 16.76(8.70,25.12)mg/g, P<0.001). 2. Linear regression analysis using the decrease in UACR values as the dependent variable demonstrated a positive linear relationship with the decrease in BMI, VFA, fasting insulin (FINS), and homeostasis model assessment of insulin resistance (HOMA-IR). Furthermore, multiple linear regression analysis indicated that the decrease in VFA (B=0.537 [95% confidence interval, 0.084 to 0.989]; P = 0.021) and HOMA-IR (B=1.000 [95% confidence interval, 0.082 to 1.917]; P = 0.033) values independently correlated with decrease in UACR values. CONCLUSIONS: PAP treatment can reduce UACR in patients with MS and OSAHS, and has the effect of improving metabolic disorders. The decrease of UACR in patients may be related to the decrease of visceral fat and the improvement of insulin resistance.

Association of Kidney Function Measures With Signs of Neurodegeneration and Small Vessel Disease on Brain Magnetic Resonance Imaging: The Atherosclerosis Risk in Communities (ARIC) Study.

RATIONALE & OBJECTIVE: Chronic kidney disease (CKD) is a risk factor for cognitive decline, but evidence is limited on its etiology and morphological manifestation in the brain. We evaluated the association of estimated glomerular filtration rate (eGFR) and urinary albumin-creatinine ratio (UACR) with structural brain abnormalities visible on magnetic resonance imaging (MRI). We also assessed whether this association was altered when different filtration markers were used to estimate GFR. STUDY DESIGN: Cross-sectional study nested in a cohort study. SETTING & PARTICIPANTS: 1,527 participants in the Atherosclerosis Risk in Communities (ARIC) Study. PREDICTORS: Log(UACR) and eGFR based on cystatin C, creatinine, cystatin C and creatinine in combination, or ß2-microglobulin (B2M). OUTCOMES: Brain volume reduction, infarcts, microhemorrhages, white matter lesions. ANALYTICAL APPROACH: Multivariable linear and logistic regression models fit separately for each predictor based on a 1-IQR difference in the predictor value. RESULTS: Each 1-IQR lower eGFR was associated with reduced cortex volume (regression coefficient: -0.07 [95% CI, -0.12 to-0.02]), greater white matter hyperintensity volume (logarithmically transformed; regression coefficient: 0.07 [95% CI, 0.01-0.15]), and lower white matter fractional anisotropy (regression coefficient: -0.08 [95% CI, -0.17 to-0.01]). The results were similar when eGFR was estimated with different equations based on cystatin C, creatinine, a combination of cystatin C and creatinine, or B2M. Higher log(UACR) was similarly associated with these outcomes as well as brain infarcts and microhemorrhages (odds ratios per 1-IQR-fold greater UACR of 1.31 [95% CI, 1.13-1.52] and 1.30 [95% CI, 1.12-1.51], respectively). The degree to which brain volume was lower in regions usually susceptible to Alzheimer disease and LATE (limbic-predominant age-related TDP-43 [Tar DNA binding protein 43] encephalopathy) was similar to that seen in the rest of the cortex. LIMITATIONS: No inference about longitudinal effects due to cross-sectional design. CONCLUSIONS: We found eGFR and UACR are associated with structural brain damage across different domains of etiology, and eGFR- and UACR-related brain atrophy is not selective for regions typically affected by Alzheimer disease and LATE. Hence, Alzheimer disease or LATE may not be leading contributors to neurodegeneration associated with CKD.

Nonalbuminuric Diabetic Kidney Disease and Risk of All-Cause Mortality and Cardiovascular and Kidney Outcomes in Type 2 Diabetes: Findings From the Hong Kong Diabetes Biobank.

RATIONALE & OBJECTIVE: Nonalbuminuric diabetic kidney disease (DKD) has become the prevailing DKD phenotype. We compared the risks of adverse outcomes among patients with this phenotype compared with other DKD phenotypes. STUDY DESIGN: Multicenter prospective cohort study. SETTINGS & PARTICIPANTS: 19,025 Chinese adults with type 2 diabetes enrolled in the Hong Kong Diabetes Biobank. EXPOSURES: DKD phenotypes defined by baseline estimated glomerular filtration rate (eGFR) and albuminuria: no DKD (no decreased eGFR or albuminuria), albuminuria without decreased eGFR, decreased eGFR without albuminuria, and albuminuria with decreased eGFR. OUTCOMES: All-cause mortality, cardiovascular disease (CVD) events, hospitalization for heart failure (HF), and chronic kidney disease (CKD) progression (incident kidney failure or sustained eGFR reduction ≥40%). ANALYTICAL APPROACH: Multivariable Cox proportional or cause-specific hazards models to estimate the relative risks of death, CVD, hospitalization for HF, and CKD progression. Multiple imputation was used for missing covariates. RESULTS: Mean participant age was 61.1 years, 58.3% were male, and mean diabetes duration was 11.1 years. During 54,260 person-years of follow-up, 438 deaths, 1,076 CVD events, 298 hospitalizations for HF, and 1,161 episodes of CKD progression occurred. Compared with the no-DKD subgroup, the subgroup with decreased eGFR without albuminuria had higher risks of all-cause mortality (hazard ratio [HR], 1.59 [95% CI, 1.04-2.44]), hospitalization for HF (HR, 3.08 [95% CI, 1.82-5.21]), and CKD progression (HR, 2.37 [95% CI, 1.63-3.43]), but the risk of CVD was not significantly greater (HR, 1.14 [95% CI, 0.88-1.48]). The risks of death, CVD, hospitalization for HF, and CKD progression were higher in the setting of albuminuria with or without decreased eGFR. A sensitivity analysis that excluded participants with baseline eGFR <30 mL/min/1.73 m2 yielded similar findings. LIMITATIONS: Potential misclassification because of drug use. CONCLUSIONS: Nonalbuminuric DKD was associated with higher risks of hospitalization for HF and of CKD progression than no DKD, regardless of baseline eGFR.

Prospective urinary albumin/creatinine ratio for diagnosis, staging, and organ response assessment in renal AL amyloidosis: results from a large cohort of patients.

OBJECTIVES: Quantification of 24 h-proteinuria is the gold standard for diagnosing, staging, and monitoring of patients with renal AL amyloidosis. However, 24 h-urine collection is cumbersome and may result in preanalytical error. In this prospective study, we investigated the role of urinary albumin/creatinine ratio (UACR) (cut-off: 300 mg/g) identifying renal involvement, evaluated a UACR-based staging system (UACR cut-off: 3,600 mg/g) and assessed whether UACR response (UACR decrease >30% without worsening in eGFR >25%) predicts renal outcome in 531 patients with newly-diagnosed AL amyloidosis. METHODS: From October 2013 paired 24 h-proteinuria and UACR (on first morning void) were measured in all newly-diagnosed patients with AL amyloidosis. Correlation between 24 h-proteinuria and UACR at baseline was assessed by Pearson's r test. Impact of UACR response on renal outcome was assessed in randomly created testing (n=354) and validation (n=177) cohorts. RESULTS: A strong linear correlation was found between 24 h-proteinuria and UACR at baseline (r=0.90; p<0.001). After a median follow-up of 31 months, 57 (11%) patients required dialysis. A UACR-based renal staging system identified three stages with significantly higher dialysis rate at 36 months comparing stage I with stage II and stage II with stage III. Achieving a renal response, according to a UACR-based criterion, resulted in lower dialysis rate in both testing and validation cohorts. CONCLUSIONS: UACR is a reliable marker for diagnosis, prognosis, and organ response assessment in renal AL amyloidosis and can reliably replace 24 h-proteinuria in clinical trials and individual patients' management.

Effect of Intensive Urate Lowering With Combined Verinurad and Febuxostat on Albuminuria in Patients With Type 2 Diabetes: A Randomized Trial.

RATIONALE & OBJECTIVE: Hyperuricemia has been implicated in the development and progression of chronic kidney disease. Verinurad is a novel, potent, specific urate reabsorption inhibitor. We evaluated the effects on albuminuria of intensive urate-lowering therapy with verinurad combined with the xanthine oxidase inhibitor febuxostat in patients with hyperuricemia and type 2 diabetes mellitus (T2DM). STUDY DESIGN: Phase 2, multicenter, prospective, randomized, double-blind, parallel-group, placebo-controlled trial. SETTING & PARTICIPANTS: Patients 18 years or older with hyperuricemia, albuminuria, and T2DM. INTERVENTION: Patients randomly assigned 1:1 to verinurad (9mg) plus febuxostat (80mg) or matched placebo once daily for 24 weeks. OUTCOMES: The primary end point was change in urinary albumin-creatinine ratio (UACR) from baseline after 12 weeks' treatment. Secondary end points included safety and tolerability and effect on glomerular filtration. RESULTS: 60 patients were enrolled (n=32, verinurad and febuxostat; n=28, placebo). UACRs after treatment with verinurad plus febuxostat were lower than after placebo at 1, 12, and 24 weeks: -38.6% (90% CI, -60.9% to-3.6%), -39.4% (90% CI, -61.8% to-3.8%), and-49.3% (90% CI, -68.2% to-19.0%), respectively. Serum urate levels after treatment with verinurad plus febuxostat were 59.6% and 63.7% lower than after placebo at 12 and 24 weeks, respectively. No clinically meaningful changes were observed in estimated glomerular filtration rate or serum creatinine or serum cystatin C concentrations. Verinurad plus febuxostat was well tolerated. LIMITATIONS: Sample size and study duration were insufficient to evaluate definitive effects of verinurad plus febuxostat on UACR and glomerular filtration. Generalizability was limited by exclusion of patients with stages 4 and 5 chronic kidney disease. CONCLUSIONS: Verinurad plus febuxostat reduced albuminuria and lowered serum urate concentrations in patients with T2DM, albuminuria, and hyperuricemia. Definitive assessment of their combined impact on preservation of kidney function awaits larger clinical studies. FUNDING: This study was supported by AstraZeneca. TRIAL REGISTRATION: Registered at ClinicalTrials.gov with study number NCT03118739.

Relative and Absolute Risk Reductions in Cardiovascular and Kidney Outcomes With Canagliflozin Across KDIGO Risk Categories: Findings From the CANVAS Program.

RATIONALE & OBJECTIVE: Canagliflozin reduces the risk for cardiovascular and kidney outcomes in type 2 diabetes. This study aimed to assess the relative and absolute effects of canagliflozin on clinical outcomes across different KDIGO (Kidney Disease: Improving Global Outcomes) risk categories based on estimated glomerular filtration rate (eGFR) and urinary albumin-creatinine ratio. STUDY DESIGN: Post hoc analysis of the CANagliflozin cardioVascular Assessment Study (CANVAS) Program. SETTINGS & PARTICIPANTS: The CANVAS Program randomly assigned 10,142 participants with type 2 diabetes at high cardiovascular risk and with eGFR≥30mL/min/1.73m2 to treatment with canagliflozin or placebo. INTERVENTION(S): Canagliflozin or matching placebo. OUTCOMES: The primary outcome was a composite of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke, with a set of other cardiovascular and kidney prespecified outcomes. RESULTS: Of 10,142 participants, 10,031 (98.9%) had available baseline eGFR and urinary albumin-creatinine ratio data. The proportion of participants in low-, moderate-, high-, and very high-risk KDIGO categories was 58.6%, 25.8%, 10.6%, and 5.0%, respectively. The relative effect of canagliflozin on the primary outcome (HR, 0.86; 95% CI, 0.75-0.97) was consistent across KDIGO risk categories (P trend=0.2), with similar results for other cardiovascular and kidney outcomes. Absolute reductions in the primary outcome were greater within higher KDIGO risk categories (P trend=0.03) with a similar pattern of effect for the composite of cardiovascular death or hospitalization for heart failure (P trend=0.06) and for chronic eGFR slope (P trend = 0.04). LIMITATIONS: Predominantly a low kidney risk population, relatively few participants in higher KDIGO risk categories, and exclusion of individuals with eGFR<30mL/min/1.73m2. CONCLUSIONS: Although the relative effects of canagliflozin are similar across KDIGO risk categories, absolute risk reductions are likely greater for individuals at higher KDIGO risk. The KDIGO classification system may be able to identify individuals who might derive greater benefits for end-organ protection from treatment with canagliflozin. FUNDING: This post hoc analysis was not specifically funded. The original CANVAS Program trials were funded by Janssen Research & Development, LLC and were conducted as a collaboration between the funder, an academic steering committee, and an academic research organization, George Clinical. TRIAL REGISTRATION: The original trials of the CANVAS Program were registered at ClinicalTrials.gov with study numbers NCT01032629 and NCT01989754.

Kidney Function as Risk Factor and Predictor of Cardiovascular Outcomes and Mortality Among Older Adults.

RATIONALE & OBJECTIVE: Estimated glomerular filtration rate (eGFR) and urinary albumin-creatinine ratio (UACR) are associated with cardiovascular events in the general population but their utility among older adults is unclear. We investigated the associations of eGFR and UACR with stroke, myocardial infarction (MI), and death among older adults. STUDY DESIGN: Population-based cohort study. SETTING & PARTICIPANTS: 1,581 participants (aged≥70 years) in the Berlin Initiative Study (BIS) without prior stroke or MI. EXPOSURES & PREDICTORS: Serum creatinine- and cystatin C-based eGFR, UACR categories, and measured GFR (n=436). OUTCOMES: Stroke, MI, and all-cause mortality. ANALYTICAL APPROACH: HRs and 95% CIs derived from multivariable-adjusted Cox proportional hazards models for association analyses. Net reclassification improvement (NRI) and C statistic differences comparing the predictive benefit of kidney measures with a traditional cardiovascular risk model. RESULTS: During a median follow-up of 8.2 years, 193 strokes, 125 MIs, and 531 deaths occurred. Independent of UACR, when GFR was estimated using the creatinine- and cystatin C-based BIS equation, eGFR of 45 to 59mL/min/1.73m2 (vs eGFR>60mL/min/1.73m2) was associated with stroke (HR, 2.23; 95% CI, 1.55-3.21) but not MI or all-cause mortality. For those with eGFR<45mL/min/1.73m2, the HRs were 1.99 (95% CI, 1.23-3.20) for stroke, 1.38 (95% CI, 0.81-2.36) for MI, and 1.57 (95% CI, 1.20-2.06) for mortality. Compared with UACR<30mg/g, UACR of 30 to 300mg/g was not associated with stroke (HR, 0.91; 95% CI, 0.63-1.33) but was associated with MI (HR, 1.65; 95% CI, 1.09-2.51) and all-cause mortality (HR, 1.63; 95% CI, 1.34-1.98). Prediction analysis for stroke showed significant positive NRI for eGFR calculated using the cystatin C-based Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation and the creatinine- and cystatin C-based BIS and Full Age Spectrum equations. UACR demonstrated significant positive NRIs for MI and mortality. LIMITATIONS: eGFR and UACR categorization based on single assessments; lack of cause-specific death data. CONCLUSIONS: eGFR of 45 to 59mL/min/1.73m2 without albuminuria was associated with stroke but not MI or all-cause mortality in older adults. In contrast, UACR of 30 to 300mg/g was associated with MI and all-cause mortality but not with stroke. Furthermore, cystatin C-based eGFR improved risk prediction for stroke in this cohort of older adults.

The retinopathy-derived HbA1c threshold of 6.5% for type 2 diabetes also captures the risk of diabetic nephropathy in NHANES.

AIM: To determine if an HbA1c diagnostic threshold of less than 6.5% (<48 mmol/mol) could be identified based on a urinary albumin-creatinine ratio (UACR) of 30 mg/g or higher in subjects not known to have diabetes. METHODS: A UACR was measured for 20 158 participants in the 2011-2018 nationally representative cross-sectional National Health and Nutrition Examination Surveys (NHANES; cycles 7-10 inclusive). RESULTS: There was a significant trend for an increasing risk with a UACR of 30 mg/g or higher across increasing HbA1c categories (P < .0001). This trend was mainly attributable to the high prevalence of raised UACR in the 7.0% or higher HbA1c subgroup of subjects not previously diagnosed with diabetes. None of the odds ratios in the lower HbA1c subgroups versus the HbA1c subgroup of less than 5.0% reached significance. There were racial/ethnic differences in UACR risk (P < .0001), with White and Black subjects exhibiting little increased risk (vs. HbA1c <5.0%) until they reached an HbA1c of 7.0%, while Asian and Hispanic subjects showed some increased, but non-significant, risks at lower HbA1c levels. Maximizing the area under receiver operating characteristic curves from logistic regressions predicted an ideal HbA1c threshold of 5.8%, but there was little variation in area from 5.5% to 7.0%. CONCLUSION: A clinically useful diagnostic threshold below 6.5% for HbA1c for elevated UACR risk was not identified, with an increased risk only obvious at an HbA1c of 7.0% or higher. Thus, the retinopathy-derived HbA1c threshold of 6.5% also captures the risk of diabetic nephropathy in NHANES.

Triglycerides to high-density lipoprotein cholesterol ratio is superior to triglycerides and other lipid ratios as an indicator of increased urinary albumin-to-creatinine ratio in the general population of China: a cross-sectional study.

BACKGROUND: Dyslipidemia contributes to the pathogenesis of renal dysfunction. Previous research demonstrated that triglycerides (TG), instead of other individual lipid indexes, has a significant link with elevated urinary albumin-to-creatinine ratio (UACR). However, it is unclear whether lipid ratios are superior indicators of increased UACR compared with TG. This research is to determine whether there are close relationships of lipid ratios with UACR in a general population. METHODS: 35,751 participants from seven centers across China were enrolled. UACR equal or higher than 30 mg/g was recognized as increased albuminuria. The associations of TG, low-density lipoprotein cholesterol (LDL-C)/ high-density lipoprotein cholesterol (HDL-C), TG/HDL-C and non-high-density lipoprotein cholesterol (non-HDL-C)/HDL-C with increased UACR were evaluated by linear and logistic regression analyses in females and males separately. RESULTS: There were 3692 (14.8%) female subjects, and 1307 (12.0%) male subjects characterized as having increased UACR. There were significantly differences in TG/HDL-C and non-HDL-C/HDL-C between the normal UACR group and the increased UACR group, while LDL-C/HDL-C was not. Furthermore, linear regression analysis was implemented and showed that TG and TG/HDL-C were both positively related to UACR even after a variety of potential confounders were adjusted regardless of sexes, while the correlation between non-HDL-C/HDL-C and elevated UACR were only significant in females. Further analyses utilizing logistic regression demonstrated that compared with non-HDL-C/HDL-C and TG, TG/HDL-C showed the strongest association with increased UACR (quartile 1 of TG/HDL-C as a reference; OR [95% CI] of quartile 4: 1.28 [1.13-1.44] in women, 1.24 [1.02-1.50] in men) after fully adjusting for potential confounding factors. Stratified analyses revealed that in males who were overweight and in females who were overweight or over 55 years or had prediabetes or prehypertension, TG/HDL-C had significant associations with abnormal UACR. CONCLUSIONS: Compared with TG and other routine lipid ratios, TG/HDL-C is a superior indicator for increased UACR.

CKD Awareness Among US Adults by Future Risk of Kidney Failure.

RATIONALE & OBJECTIVE: Persons with chronic kidney disease (CKD) are often unaware of their disease status. Efforts to improve CKD awareness may be most effective if focused on persons at highest risk for progression to kidney failure. STUDY DESIGN: Serial cross-sectional surveys. SETTING & PARTICIPANTS: Nonpregnant adults (aged≥20 years) with CKD glomerular filtration rate categories 3-4 (G3-G4) who participated in the National Health and Nutrition Examination Survey from 1999 to 2016 (n = 3,713). PREDICTOR: 5-year kidney failure risk, estimated using the Kidney Failure Risk Equation. Predicted risk was categorized as minimal (<2%), low (2%-<5%), intermediate (5%-<15%), or high (≥15%). OUTCOME: CKD awareness, defined by answering "yes" to the question "Have you ever been told by a doctor or other health professional that you had weak or failing kidneys?" ANALYTICAL APPROACH: Prevalence of CKD awareness was estimated within each risk group using complex sample survey methods. Associations between Kidney Failure Risk Equation risk and CKD awareness were assessed using multivariable logistic regression. CKD awareness was compared with awareness of hypertension and diabetes during the same period. RESULTS: In 2011 to 2016, unadjusted CKD awareness was 9.6%, 22.6%, 44.7%, and 49.0% in the minimal-, low-, intermediate-, and high-risk groups, respectively. In adjusted analyses, these proportions did not change over time. Awareness of CKD, including among the highest risk group, remains consistently below that of hypertension and diabetes and awareness of these conditions increased over time. LIMITATIONS: Imperfect sensitivity of the "weak or failing kidneys" question for ascertaining CKD awareness. CONCLUSIONS: Among adults with CKD G3-G4 who have 5-year estimated risks for kidney failure of 5%-<15% and≥15%, approximately half were unaware of their kidney disease, a gap that has persisted nearly 2 decades.

Fenofibrate decreased microalbuminuria in the type 2 diabetes patients with hypertriglyceridemia.

BACKGROUND: This study was to research the efficacy of fenofibrate in the treatment of microalbuminuria in the patients with type 2 diabetes mellitus (T2DM) and hypertriglyceridemia. METHODS: Type 2 diabetic patients (56) with microalbuminuria and hypertriglyceridemia aged 30 to 75 were randomly divided into the fenofibrate treatment group(n = 28) and the control group (n = 28) for 180 days. Urinary microalbumin /creatinine ratio (UACR) and other metabolic parameters were compared at baseline, during treatment and after treatment. RESULTS: After 180 days, the reduction of level of fasting blood glucose (FBG) and glycosylated hemoglobin (HbA1c) between two groups showed no difference. In the treatment group, uric acid (UA) (296.42 ± 56.41 vs 372.46 ± 72.78), triglyceride (TG) [1.51(1.17, 2.06) vs 3.04(2.21, 3.29)], and UACR [36.45 (15.78,102.41) vs 129.00 (53.00, 226.25)] were significantly decreased compared with the baseline. The high-density lipoprotein cholesterol (HDL-C) levels were significantly increased (1.22 ± 0.26 vs 1.09 ± 0.24) compared with the baseline. The decrease in UACR [- 44.05(- 179.47, - 12.16) vs - 8.15(- 59.69, 41.94)]in treatment group was significantly higher compared with the control group. The decrease in UACR was positively associated with the decreases in TG (r = 0.447, P = 0.042) and UA (r = 0.478, P = 0.024) after fenofibrate treatment. CONCLUSION: In the patients with hypertriglyceridemia and type 2 diabetes mellitus, fenofibrate can improve microalbuminuria and do not increase the deterioration of glomerular filtration rate. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02314533, 2014.12.9.

Association of diabetic nephropathy with the severity of obstructive sleep apnea-hypopnea syndrome in patients with type 2 diabetes mellitus.

This study aimed to analyze the effect of the severity of obstructive sleep apnea-hypopnea syndrome (OSAHS) on diabetic nephropathy (DN) in patients with type 2 diabetes mellitus (T2DM). A total of 322 patients with T2DM participated in this cross-sectional study. OSAHS was diagnosed according to the apnea-hypopnea index (AHI) and it was categorized as follows: normal, mild, moderate, and severe. Relevant clinical data retrieved from medical charts were cross-analyzed between different groups. The relationship between urinary albumin/creatinine ratio(UACR) and OSAHS parameters, which included AHI, lowest oxygen saturation (L-SaO2), and mean oxygen saturation (M-SaO2), was evaluated by partial correlation analysis. DN stages were classified into a non-DN group, a microalbuminuria group, and a macroalbuminuria group. Multiple factor logistic regression analysis was employed to analyze factors influencing DN. The results showed that mild OSAHS, moderate OSAHS, and severe OSAHS patients had a higher Body mass index (BMI), creatinine (CR) level, UACR, and a longer duration of T2DM (p < 0.05) than the non-OSAHS group. The prevalence of DN in the non-OSAHS, mild OSAHS, moderate OSAHS, and severe OSAHS groups was 18.4%, 19.2%, 34.6%, and 49.4%, respectively (p < 0.05). Multiple factor logistic regression analysis revealed that systolic blood pressure (SBP) (OR = 1.03), AHI (OR = 1.02), and duration of T2DM (OR = 1.04) were correlated with DN (p < 0.05). These findings revealed that OSAHS is highly prevalent in T2DM and AHI is independently associated with the presence of DN.

Albuminuria and Allograft Failure, Cardiovascular Disease Events, and All-Cause Death in Stable Kidney Transplant Recipients: A Cohort Analysis of the FAVORIT Trial.

RATIONALE & OBJECTIVE: Cardiovascular disease (CVD) is common and overall graft survival is suboptimal among kidney transplant recipients. Although albuminuria is a known risk factor for adverse outcomes among persons with native chronic kidney disease, the relationship of albuminuria with cardiovascular and kidney outcomes in transplant recipients is uncertain. STUDY DESIGN: Post hoc longitudinal cohort analysis of the Folic Acid for Vascular Outcomes Reduction in Transplantation (FAVORIT) Trial. SETTING & PARTICIPANTS: Stable kidney transplant recipients with elevated homocysteine levels from 30 sites in the United States, Canada, and Brazil. PREDICTOR: Urine albumin-creatinine ratio (ACR) at randomization. OUTCOMES: Allograft failure, CVD, and all-cause death. ANALYTICAL APPROACH: Multivariable Cox models adjusted for age; sex; race; randomized treatment allocation; country; systolic and diastolic blood pressure; history of CVD, diabetes, and hypertension; smoking; cholesterol; body mass index; estimated glomerular filtration rate (eGFR); donor type; transplant vintage; medications; and immunosuppression. RESULTS: Among 3,511 participants with complete data, median ACR was 24 (Q1-Q3, 9-98) mg/g, mean eGFR was 49±18 (standard deviation) mL/min/1.73m2, mean age was 52±9 years, and median graft vintage was 4.1 (Q1-Q3, 1.7-7.4) years. There were 1,017 (29%) with ACR < 10mg/g, 912 (26%) with ACR of 10 to 29mg/g, 1,134 (32%) with ACR of 30 to 299mg/g, and 448 (13%) with ACR ≥ 300mg/g. During approximately 4 years, 282 allograft failure events, 497 CVD events, and 407 deaths occurred. Event rates were higher at both lower eGFRs and higher ACR. ACR of 30 to 299 and ≥300mg/g relative to ACR < 10mg/g were independently associated with graft failure (HRs of 3.40 [95% CI, 2.19-5.30] and 9.96 [95% CI, 6.35-15.62], respectively), CVD events (HRs of 1.25 [95% CI, 0.96-1.61] and 1.55 [95% CI, 1.13-2.11], respectively), and all-cause death (HRs of 1.65 [95% CI, 1.23-2.21] and 2.07 [95% CI, 1.46-2.94], respectively). LIMITATIONS: No data for rejection; single ACR assessment. CONCLUSIONS: In a large population of stable kidney transplant recipients, elevated baseline ACR is independently associated with allograft failure, CVD, and death. Future studies are needed to evaluate whether reducing albuminuria improves these outcomes.

Long-term Association of Periodontitis With Decreased Kidney Function.

RATIONALE & OBJECTIVE: Previous studies have yielded inconclusive findings regarding the relationship between periodontitis and kidney function. We sought to investigate whether periodontitis is associated with subsequent decreases in kidney function (reductions in estimated glomerular filtration rate [eGFR] and increased urinary albumin-creatinine ratio [UACR]) in the general population. STUDY DESIGN: Population-based cohort study. SETTING & PARTICIPANTS: We used baseline and 11-year follow-up data from 2,297 and 1,512 adult participants, respectively, in the Study of Health in Pomerania (SHIP). Age range was limited to 20 to 59 years to avoid the potential influence of tooth loss. EXPOSURES: Periodontal status defined by periodontal pocket probing depth (PPD) and clinical attachment level. Mean levels and the percentage of sites ≥ 3mm was determined for either all sites (PPD) or interproximal sites (clinical attachment level). All PPDs≥4mm were summed to calculate the total PPD. OUTCOMES: GFR estimated from serum creatinine and serum cystatin C (eGFRcr-cys). Moderately increased albuminuria defined as UACR>30mg/g. ANALYTICAL APPROACH: Adjusted linear and logistic mixed regression models. RESULTS: At baseline and follow-up, average eGFRcr-cys was 118.3 and 105.0mL/min/1.73m2, respectively. Using mixed models, no consistently significant associations between periodontitis variables and eGFRcr-cys were detected. Long-term changes in UACR were inconsistently associated with periodontitis measures. After imputation of missing data, associations were either attenuated or no longer detectable. LIMITATIONS: Because periodontal assessments were performed using a partial recording protocol, periodontal disease severity estimates might have been underestimated, resulting in attenuated effect estimates. CONCLUSIONS: We found no consistent evidence for an association between periodontitis and decreased kidney function. In contrast to previous studies, these results do not support the hypothesis that periodontitis is an important risk factor for chronic kidney disease.

The Association Between Kidney Disease and Diabetes Remission in Bariatric Surgery Patients With Type 2 Diabetes.

RATIONALE & OBJECTIVE: The association between bariatric surgery, type 2 diabetes, and chronic kidney disease (CKD) is poorly understood. We studied whether remission of type 2 diabetes induced by bariatric surgery influences markers of kidney disease, if CKD is associated with remission of diabetes after bariatric surgery, and if baseline levels of gut hormones and peptides modify these associations. STUDY DESIGN: Prospective observational study. STUDY PARTICIPANTS: 737 bariatric surgery patients with type 2 diabetes who participated in a multicenter cohort study for up to 5 years. PREDICTORS: Demographics, blood pressure, medications, type of bariatric surgery, anthropometrics, markers of kidney disease, and circulating levels of gut hormones and peptides. OUTCOMES: Estimated glomerular filtration rate (eGFR), urinary albumin excretion, prognostic risk for CKD, and remission of diabetes. ANALYTICAL APPROACH: Linear mixed models for eGFR; generalized linear mixed models with logit link for albuminuria, prognostic risk for CKD, and diabetes remission. RESULTS: Remission of diabetes at 5 years post-bariatric surgery was not independently associated with eGFR but was associated with lower risk for moderate/severe increase in albuminuria (risk ratio, 0.66; 95% CI, 0.48-0.90) and stabilization in prognostic risk for CKD. These findings were modified by baseline ghrelin level. Lower preoperative eGFR and greater prognostic risk for CKD were independently associated with reduced likelihood of diabetes remission. The association with preoperative GFR was modified by C-peptide level. Higher baseline circulating ghrelin level was independently associated with a lower prognostic risk for CKD. LIMITATIONS: A minority of participants had baseline CKD; lack of comparison group; no information on duration of diabetes, other clinical end points, or kidney biopsy results. CONCLUSIONS: Remission of type 2 diabetes 5 years after bariatric surgery was associated with improvements in albuminuria and stabilized prognostic risk for CKD, but not with eGFR. Lower kidney function and greater prognostic risk at the time of bariatric surgery was linked to a lower likelihood of diabetes remission. These results highlight the need to identify the mechanisms through which bariatric surgery may delay the long-term progression of CKD in type 2 diabetes.

Impact of Kidney Function on Cardiovascular Risk and Mortality: A Comparison of South Asian and European Cohorts.

BACKGROUND: Evidence is limited on ethnic differences in associations between kidney function markers and mortality or cardiovascular disease (CVD). METHODS: Baseline cross-sectional analysis and longitudinal follow-up study of a UK population-based cohort of 1,116 Europeans and 1,104 South Asians of predominantly Indian descent, age 52 ± 7 years at baseline (1988-1991). Kidney function was estimated using Cystatin C and creatinine-based chronic kidney disease (CKD) Epidemiology Collaboration estimated glomerular filtration rate (eGFR) equations, and urinary albumin-creatinine ratio (ACR). Mortality was captured at 27 years, and incident CVD at 22 years, from death certification, medical records and participant report. Longitudinal associations between eGFR/ACR and mortality/incident CVD were examined using Cox models. RESULTS: eGFRcys was lower and ACR higher in South Asians than Europeans. eGFRcys and -eGFRcreat were more strongly associated with outcomes in Europeans than South Asians. Conversely, associations between ACR and outcomes were greater in South Asians than Europeans, for example, for CVD mortality: HRs (95% CI) adjusted for CVD risk factors and ACR/eGFRcys as appropriate, p for ethnicity interaction: eGFRcys: Europeans: 0.76 (0.62-0.92), South Asians: 0.92 (0.78-1.07), p = 0.05, eGFRcreat: Europeans 0.81 (0.67-0.99), South Asians 1.18 (0.97-1.41), p = 0.002, ACR: -Europeans: 1.24 (1.08-1.42), South Asians: 1.39 (1.25-1.57), p= 0.23. Addition of all CKD measures to a standard CVD risk factor model modestly improved prediction capability in -Europeans; in South Asians only ACR contributed to improvement. CONCLUSIONS: Strong associations between ACR and outcomes in South Asians of predominantly Indian origin, and null associations for eGFRcys and eGFRcreat, suggest that ACR may have greater utility in CVD risk prediction in South Asians. Further work is needed to validate these -findings.

Biological Variability of Estimated GFR and Albuminuria in CKD.

RATIONALE & OBJECTIVE: Determining whether a change in estimated glomerular filtration rate (eGFR) or albuminuria is clinically significant requires knowledge of short-term within-person variability of the measurements, which few studies have addressed in the setting of chronic kidney disease. STUDY DESIGN: Cross-sectional study with multiple collections over less than 4 weeks. SETTING & PARTICIPANTS: Clinically stable outpatients with chronic kidney disease (N=50; mean age, 56.8 years; median eGFR, 40mL/min/1.73m2; median urinary albumin-creatinine ratio (UACR), 173mg/g). EXPOSURE: Repeat measurements from serially collected samples across 3 study visits. OUTCOMES: Measurements of urine albumin concentration (UAC), UACR, and plasma creatinine, cystatin C, ß2-microglobulin (B2M), and beta trace protein (BTP). ANALYTICAL APPROACH: We calculated within-person coefficients of variation (CVw) values and corresponding reference change positive and negative (RCVpos and RCVneg) values using log-transformed measurements. RESULTS: Median CVw (RCVpos; RCVneg) values of filtration markers were 5.4% (+16%; -14%) for serum creatinine, 4.1% (+12%; -11%) for cystatin C, 7.4% (+23%; -18%) for BTP, and 5.6% (+17%; -14%) for B2M. Results for albuminuria were 33.2% (+145%; -59%) for first-morning UAC, 50.6% (+276%; -73%) for random spot UAC, 32.5% (+141%; -58%) for first-morning UACR, and 29.7% (124%; -55%) for random spot UACR. CVw values for filtration markers were comparable across the range of baseline eGFRs. CVw values for UAC and UACR were comparable across the range of baseline albuminuria values. LIMITATIONS: Small sample size limits the ability to detect differences in variability across markers. Participants were recruited and followed up in a clinical and not research setting, so some preanalytical factors could not be controlled. CONCLUSIONS: eGFR markers appear to have relatively low short-term within-person variability, whereas variability in albuminuria appears to be high, making it difficult to distinguish random variability from meaningful biologic changes.

Greater Dietary Inflammatory Index score is associated with higher likelihood of chronic kidney disease.

Chronic kidney disease (CKD) is described as a progressive alteration of kidney function, resulting from multiple factors, including behaviours. We investigated the association of the Dietary Inflammatory Index (DII®) with prevalent CKD in adult Americans. National Health and Nutrition Examination Survey participants with measured data on kidney function markers from 2005 to 2012 were included in this study. Prevalent CKD was based on an estimated glomerular filtration rate (eGFR) <60 ml/min per 1·73 m2 or urinary albumin/creatinine≥30 mg/g. Energy-adjusted DII (E-DIITM) scores were calculated from 24-h dietary recalls. Statistical analyses accounted for the survey design and sample weights. We included 21 649 participants, with 1634 (6·8 %) having prevalent CKD. Participants with high E-DII scores had greater BMI, fasting blood glucose and systolic blood pressure, and were more likely to be diabetic or hypertensive (all P<0·001) compared with those with lower E-DII scores. In regression models adjusted for age, sex, race, fasting blood glucose, blood pressure, BMI, hypertension and diabetes status, mean eGFR significantly decreased across increasing quartiles of E-DII, whereas serum uric acid level and log urinary albumin:creatinine ratio significantly increased (all P<0·001). Prevalent CKD increased from 5·3 % in the lowest to 9·3 % in the highest E-DII quartile (P=0·02). In multivariable-adjusted logistic regression models, the odds of prevalent CKD were 29 % higher in the highest compared with the lowest E-DII quartile. Pro-inflammatory diet is associated with declining kidney function and high prevalence of CKD. Dietary changes that reduce inflammation have a potential to prevent CKD.

Associations between microalbuminuria and parameters of flow-mediated vasodilatation obtained by continuous measurement approaches.

The associations between microalbuminuria and various parameters of flow-mediated vasodilatation (FMD) are not completely understood. We retrospectively analyzed 265 consecutive patients who underwent coronary angiography and in whom we could measure FMD and the urine albumin-creatinine ratio (UACR). Using 15 continuous measurement approaches, we measured FMD as the magnitude of the percentage change in the brachial artery diameter from baseline to peak (bFMD), the maximum FMD rate calculated as the maximal slope of dilation (FMD-MDR), and the integrated FMD response calculated as the area under the dilation curve during the 60- and 120-s dilation periods (FMD-AUC60 and FMD-AUC120). We divided the patients into two groups according to UACR: normoalbuminuria (NOR, n = 211) and microalbuminuria (MIC, n = 54). The MIC group showed a significantly higher percentage of coronary artery disease than the NOR group. FMD-AUC60 and FMD-AUC120, but not FMD-MDR, in the MIC group were significantly lower than those in the NOR group. On the other hand, bFMD in the MIC group tended to be lower than that in the NOR group, but this difference was not significant. A multiple regression analysis indicated that FMD-AUC120 and diabetes mellitus were predictors of MIC. Finally, we defined the cut-off value of FMD-AUC120 for the presence of MIC in all patients as 8.4 mm x second (sensitivity 0.640, specificity 0.588) by a receiver-operating characteristic curve analysis. In conclusion, this study provides more definitive evidence for the association of microalbuminuria with endothelial dysfunction. FMD-AUC120 may be a superior marker for MIC.

Association of body mass index and weight gain patterns with albumin excretion in pregnancy.

AIM: We examined body mass index (BMI) and gestational weight gain (GWG) patterns of pregnant women and investigated the impact of these factors on the urinary albumin-creatinine ratio (ACR) during pregnancy. METHODS: The data of 163 women whose basal BMI and ACR were measured during the first trimester were used in this study. Body weight alone between 12-16 weeks and body weight together with ACR after 37 weeks of gestation were measured. RESULTS: Overall, 46% of women were overweight or obese, 60.7% had excessive weight gain and 16.6% had inadequate weight gain. Only 22.7% of women gained weight within the recommended range. There was no difference in weight gain patterns with respect to BMI. ACR during the third trimester was significantly higher than during the first trimester (7.08 [0.00-1180.90] mg/g vs 4.73 [0.00-275.00] mg/g, respectively; P = 0.001). The ACR of obese women was higher than in normal weight subjects during the third trimester (16.79 mg/g [0.01-1180.90] vs 8.07 mg/g [0.10-402.14] respectively; adjusted P = 0.015). Both ACR change and third trimester ACR were weakly but significantly correlated with basal BMI (r: 0.228 P: 0.003 and r: 0.301 P < 0.001, respectively) but not with GWG or GWG rate. Basal BMI was not associated with first-trimester ACR. CONCLUSION: Obesity is associated with an increase in urinary albumin excretion during the course of pregnancy. Distinction of this relationship during pregnancy offers an opportunity for further research on pathophysiological mechanisms. The alarmingly high rate of non-compliance with IOM guidelines in pregnant women is a concern. Prompt measures for counseling of women before and during pregnancy in order to maintain healthy weight are needed.